OPT: A New Framework for Overlapped and Parallel Triangulation in Large-scale Graphs

Graph triangulation, which finds all triangles in a graph, has been actively studied due to its wide range of applications in the network analysis and data mining. With the rapid growth of graph data size, disk-based triangulation methods are in demand but little researched. To handle a large-scale graph which does not fit in memory, we must iteratively load small parts of the graph. In the existing literature, achieving the ideal cost has been considered to be impossible for billion-scale graphs due to the memory size constraint. In this paper, we propose an overlapped and parallel disk-based triangulation framework for billion-scale graphs, OPT, which achieves the ideal cost by (1) full overlap of the CPU and :1/0 operations and (2) full parallelism of multi-core CPU and FlashSSD I/O. In OPT, triangles in memory are called the internal triangles while triangles constituting vertices in memory and vertices in external memory are called the external triangles. At the macro level, OPT overlaps the internal triangulation and the external triangulation, while it overlaps the CPU and I/O operations at the micro level. Thereby, the cost of OPT is close to the ideal cost. Moreover, OPT instantiates both vertex-iterator and edge-iterator models and benefits from multi-thread parallelism on both types of triangulation. Extensive experiments conducted on large-scale datasets showed that (1) OPT achieved the elapsed time close to that of the ideal method with less than 7% of overhead under the limited memory budget, (2) OPT achieved linear speed-up with an increasing number of CPU cores, (3) OPT outperforms the state-ofthe-art parallel method by up to an order of magnitude with 6 CPU cores, and (4) for the first time in the literature, the triangulation results are reported for a billion-vertex scale real-world graph.ungraded1121sciescopu

Structure-Activity Relationships of Acyclic Selenopurine Nucleosides as Antiviral Agents

A series of acyclic selenopurine nucleosides 3a–f and 4a–g were synthesized based on the bioisosteric rationale between oxygen and selenium, and then evaluated for antiviral activity. Among the compounds tested, seleno-acyclovir (4a) exhibited the most potent anti-herpes simplex virus (HSV)-1 (EC50 = 1.47 µM) and HSV-2 (EC50 = 6.34 µM) activities without cytotoxicity up to 100 µM, while 2,6-diaminopurine derivatives 4e–g exhibited significant anti-human cytomegalovirus (HCMV) activity, which is slightly more potent than the guanine derivative 4d, indicating that they might act as prodrugs of seleno-ganciclovir (4d)

TurboGraph: A Fast Parallel Graph Engine Handling Billion-scale Graphs in a Single PC

11scopu

Design, Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives Targeting hA₁ and hA₃ Adenosine Receptor

Adenosine mediates various physiological activities in the body. Adenosine receptors (ARs) are widely expressed in tumors and the tumor microenvironment (TME), and they induce tumor proliferation and suppress immune cell function. There are four types of human adenosine receptor (hARs): hA1, hA2A, hA2B, and hA3. Both hA1 and hA3 AR play an important role in tumor proliferation. We designed and synthesized novel 1,3,5-triazine derivatives through amination and Suzuki coupling, and evaluated them for binding affinities to each hAR subtype. Compounds 9a and 11b showed good binding affinity to both hA1 and hA3 AR, while 9c showed the highest binding affinity to hA1 AR. In this study, we discovered that 9c inhibits cell viability, leading to cell death in lung cancer cell lines. Flow cytometry analysis revealed that 9c caused an increase in intracellular reactive oxygen species (ROS) and a depolarization of the mitochondrial membrane potential. The binding mode of 1,3,5-triazine derivatives to hA1 and hA3 AR were predicted by a molecular docking study

Legislative Documents

Also, variously referred to as: House bills; House documents; House legislative documents; legislative documents; General Court documents

Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells

Although RNA-guided genome editing via the CRISPR-Cas9 system is now widely used in biomedical research, genome-wide target specificities of Cas9 nucleases remain controversial. Here we present Digenome-seq, in vitro Cas9-digested whole-genome sequencing, to profile genome-wide Cas9 off-target effects in human cells. This in vitro digest yields sequence reads with the same 5' ends at cleavage sites that can be computationally identified. We validated off-target sites at which insertions or deletions were induced with frequencies below 0.1%, near the detection limit of targeted deep sequencing. We also showed that Cas9 nucleases can be highly specific, inducing off-target mutations at merely several, rather than thousands of, sites in the entire genome and that Cas9 off-target effects can be avoided by replacing 'promiscuous' single guide RNAs (sgRNAs) with modified sgRNAs. Digenome-seq is a robust, sensitive, unbiased and cost-effective method for profiling genome-wide off-target effects of programmable nucleases including Cas9.

Structure-Guided Modification of Heterocyclic Antagonists of the P2Y₁₄ Receptor

The P2Y₁₄ receptor (P2Y₁₄R) mediates inflammatory activity by activating neutrophil motility, but few classes of antagonists are known. We have explored the structure–activity relationship of a 3-(4-phenyl-1<i>H</i>-1,2,3-triazol-1-yl)-5-(aryl)­benzoic acid antagonist scaffold, assisted by docking and molecular dynamics (MD) simulation at a P2Y₁₄R homology model. A computational pipeline using the High Throughput MD Python environment guided the analogue design. Selection of candidates was based upon ligand–protein shape and complementarity and the persistence of ligand–protein interactions over time. Predictions of a favorable substitution of a 5-phenyl group with thiophene and an insertion of a three-methylene spacer between the 5-aromatic and alkyl amino moieties were largely consistent with empirical results. The substitution of a key carboxylate group on the core phenyl ring with tetrazole or truncation of the 5-aryl group reduced affinity. The most potent antagonists, using a fluorescent assay, were a primary 3-aminopropyl congener <b>20</b> (MRS4458) and phenyl <i>p</i>-carboxamide <b>30</b> (MRS4478)

Structure-Guided Modification of Heterocyclic Antagonists of the P2Y₁₄ Receptor

The P2Y₁₄ receptor (P2Y₁₄R) mediates inflammatory activity by activating neutrophil motility, but few classes of antagonists are known. We have explored the structure–activity relationship of a 3-(4-phenyl-1<i>H</i>-1,2,3-triazol-1-yl)-5-(aryl)­benzoic acid antagonist scaffold, assisted by docking and molecular dynamics (MD) simulation at a P2Y₁₄R homology model. A computational pipeline using the High Throughput MD Python environment guided the analogue design. Selection of candidates was based upon ligand–protein shape and complementarity and the persistence of ligand–protein interactions over time. Predictions of a favorable substitution of a 5-phenyl group with thiophene and an insertion of a three-methylene spacer between the 5-aromatic and alkyl amino moieties were largely consistent with empirical results. The substitution of a key carboxylate group on the core phenyl ring with tetrazole or truncation of the 5-aryl group reduced affinity. The most potent antagonists, using a fluorescent assay, were a primary 3-aminopropyl congener <b>20</b> (MRS4458) and phenyl <i>p</i>-carboxamide <b>30</b> (MRS4478)

Structure-Guided Modification of Heterocyclic Antagonists of the P2Y₁₄ Receptor

The P2Y₁₄ receptor (P2Y₁₄R) mediates inflammatory activity by activating neutrophil motility, but few classes of antagonists are known. We have explored the structure–activity relationship of a 3-(4-phenyl-1<i>H</i>-1,2,3-triazol-1-yl)-5-(aryl)­benzoic acid antagonist scaffold, assisted by docking and molecular dynamics (MD) simulation at a P2Y₁₄R homology model. A computational pipeline using the High Throughput MD Python environment guided the analogue design. Selection of candidates was based upon ligand–protein shape and complementarity and the persistence of ligand–protein interactions over time. Predictions of a favorable substitution of a 5-phenyl group with thiophene and an insertion of a three-methylene spacer between the 5-aromatic and alkyl amino moieties were largely consistent with empirical results. The substitution of a key carboxylate group on the core phenyl ring with tetrazole or truncation of the 5-aryl group reduced affinity. The most potent antagonists, using a fluorescent assay, were a primary 3-aminopropyl congener <b>20</b> (MRS4458) and phenyl <i>p</i>-carboxamide <b>30</b> (MRS4478)